The goal of the research outlined in this proposal is to investigate the scope of using 1,3-dihalo-2- (trialkylsilyl) benzenes as 1,3-benzadiyne precursors as a general route to the benz[a]anthracene core. Using disposable tethers to render the cycloadditions intramolecular will control the regiochemistry of the benzyne cycloadditions. The benz[a]anthracene cores produced will be further elaborated into the natural products rubiginone B1, urdamycinone B, and IB-00208, which are potent antitumor compounds from the angucycline/angucyclinone family of natural products. The reaction will be investigated and will expand the scope of 1,3-benzadiyne cycloadditions by using orthogonal methods of generating the requisite benzyne intermediates. This will allow for a controlled generation and reaction of benzyne to produce appropriately functionalized benz[a]anthracene cores. Efficient chemical syntheses by flexible routes using the proposed, 3-benzadiyne methodology will provide a general synthetic strategy for the synthesis of a multitude of structurally similar angucycline/angucyclinone natural products, which have been identified as potential pharmaceuticals in the therapeutic areas of cancer, anti-bacterials, anti-virals, and enzyme inhibitors.